Background The purpose of this analysis was to compare long-term urinary, bowel, and sexual function after radical prostatectomy or external-beam radiation therapy. Methods The Prostate Cancer Outcomes Study (PCOS) enrolled 3533 men in whom prostate cancer had been diagnosed in 1994 or 1995. The current cohort comprised 1655 men in whom localized prostate cancer had been diagnosed between the ages of 55 and 74 years and who had undergone either surgery (1164 men) or radiotherapy (491 men). Functional status was assessed at baseline and at 2, 5, and 15 years after diagnosis. We used multivariable propensity scoring to compare functional outcomes according to treatment. Results Patients undergoing prostatectomy were more likely to have urinary incontinence than were those undergoing radiotherapy at 2 years (odds ratio, 6.22; 95% confidence interval [CI], 1.92 to 20.29) and 5 years (odds ratio, 5.10; 95% CI, 2.29 to 11.36). However, no significant between-group difference in the odds of urinary incontinence was noted at 15 years. Similarly, although patients undergoing prostatectomy were more likely to have erectile dysfunction at 2 years (odds ratio, 3.46; 95% CI, 1.93 to 6.17) and 5 years (odds ratio, 1.96; 95% CI, 1.05 to 3.63), no significant between-group difference was noted at 15 years. Patients undergoing prostatectomy were less likely to have bowel urgency at 2 years (odds ratio, 0.39; 95% CI, 0.22 to 0.68) and 5 years (odds ratio, 0.47; 95% CI, 0.26 to 0.84), again with no significant between-group difference in the odds of bowel urgency at 15 years. Conclusions At 15 years, no significant relative differences in disease-specific functional outcomes were observed among men undergoing prostatectomy or radiotherapy. Nonetheless, men treated for localized prostate cancer commonly had declines in all functional domains during 15 years of follow-up. (Funded by the National Cancer Institute.)

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Importance Prostate cancer treatments are associated with side effects. Understanding the side effects of contemporary approaches to management of localized prostate could inform shared decision-making. Objective To compare the harms of radical prostatectomy (RP), radiation (EBRT) and active surveillance (AS). Design The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a prospective, population-based, cohort study of men diagnosed with localized prostate cancer in 2011–2012. This study reports follow up through August 2015. Setting Patients accrued from five Surveillance Epidemiology, and End Results registry sites and the Cancer of the Prostate Strategic Urologic Research Endeavor. Participants Men < 80 years old with clinical stage cT1-2 disease, prostate specific antigen < 50 ng/mL, enrolled within six months of diagnosis, who completed a baseline survey and at least 1 follow-up survey. Exposure Treatment with RP, EBRT or AS was ascertained within one year of diagnosis. Main Outcome and Measures Patient-reported function in sexual, urinary incontinence, urinary irritative, bowel, and hormonal domains on the 26-item Expanded Prostate Cancer Index Composite (EPIC) 36 months after enrollment. Domain scores range from 0–100. Higher score indicates better function. Minimum clinically important difference defined as 10–12, 6, 5, 5, and 4, respectively. Results The cohort included 2550 men (mean age 63.8 years, 74% white, 55% intermediate or high risk), of whom 1523 (59.7%) underwent RP, 598 (23.5%) EBRT, and 429 (16.8%) AS. Men undergoing EBRT were older (mean age 68.1 vs. 61.5, p<0.001), and had worse baseline sexual function (mean EPIC domain score 52.3 vs. 65.2, p<0.001) than men undergoing RP. At 3 years, adjusted mean sexual domain score for men undergoing RP had declined more than for men undergoing EBRT (mean difference −11.9 points, 95% CI [−15.1, −8.7]). The difference in decline in sexual domain scores between EBRT and AS was not clinically significant (−4.3 points, 95% CI [−9.2, 0.7]). RP was associated with worse urinary incontinence than EBRT (−18.0 points, 95% CI [−20.5, −15.4]) or AS (−12.7 points, 95% CI [−16.0, −9.3]) and better urinary irritative symptoms compared to AS (5.2 points, 95% CI [3.2, 7.2]). No clinically significant differences for bowel or hormone function were noted beyond 12 months. No differences in global quality of life or disease-specific survival (3 deaths) were noted (99.7–100%). Conclusion and Relevance In this cohort of men with localized prostate cancer, RP was associated with a larger decline in sexual function and urinary incontinence than EBRT or AS after 3 years, and lesser urinary irritative symptoms compared to AS; however, there were no meaningful differences in bowel or hormonal function beyond 12 months and no meaningful differences in global quality of life measures. These findings may facilitate counseling regarding the comparative harms of contemporary treatments for prostate cancer.

The summary presented herein represents Part I of the two-part series dedicated to Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline discussing prognostic and treatment recommendations for patients with biochemical recurrence without metastatic disease after exhaustion of local treatment options as well as those with metastatic hormone-sensitive prostate cancer. Please refer to Part II for discussion of the management of castration-resistant disease.